4- Bromo-3-nitrotoluene

C7H6BrN02 4-bromo-3-nitrotoluene 5326-34-1 25.00 1.5740 1 10303 C7H6FN04S 2-fluoro-5-methylsulphonylnitrobenzene 453-72-5 25.00 1.4870 2... 

Chloromercuri-3-nitrotoIuene crystallises from the hot acetone extractions described above. It forms pale yellow needles, sintering at 207° C. and melting at 210° C. (eorr.). It may be converted into 4-bromo-3-nitrotoluene. The presence of 6-chloromercuri-3-nitro-toiuene in the mercuration products has also been proved. 

Diethyl oxalate (29.2 g, 0.20mol) and 4-bromo-2-nitrotoluene (21.6 g, O.lOmol) were added to a cooled solution of sodium cthoxide prepared from sodium (4.6 g, 0.20 mol) and ethanol (90 ml). The mixture was stirred overnight and then refluxed for 10 min. Water (30 ml) was added and the solution refluxed for 2h to effect hydrolysis of the pyruvate ester. The solution was cooled and concentrated in vacuo. The precipitate was washed with ether and dried. The salt was dissolved in water (300 ml) and acidified with cone. HCl. The precipitate was collected, washed with water, dried and recrystallizcd from hexane-EtOAc to give 15.2 g of product. 

This method has been applied to a large-scale preparation of 6-bromoindole, which reacts with various arylboronic acids via the Suzuki reaction to afford 6-aryhndoles fEq. 10.50. 6-Bromo-5-methoxyindole for use in the synthesis of marine bromoindole " and 5-amino-7-ethoxycarbonyhndole for use in synthesis of l//-pyrrolo[3,2-g quina2ohne ring system fEq. 10.51 " have been prepared from the appropriate o-nitrotoluene. 

Hegedus also described an efficient synthesis of 4-bromoindoIe (10) and 4-bromo-l-(4-toluenesulfonyl)indole (11) starting from 2-amino-6-nitrotoluene (9) [20]. The synthesis is lengthy but yields are good, and the method involves the Hegedus indole ring synthesis discussed later in this chapter. 

Carrera and Sheppard improved upon a Leimgruber-Batcho indole synthesis [24] to prepare 6-bromoindole (20) in excellent overall yield from 4-bromo-2-nitrotoluene [29a], and Rapoport utilized this method to synthesize 4-, 5-, 6-, and 7-bromoindole [29b]. 

Another building block, the arylamine 750, was prepared from 2-bromo-6-nitrotoluene (754) in 44% overall yield in five simple steps. Transfer hydrogenation of... 

Of numerous other preparations for which nitrile oxides have been invoked as intermediates, one of the most synthetically useful is that developed by Shimizu et al. which employs alkyl esters of a-nitroalkanoic acids as precursors <87BCJ1948). The method is suitable for aliphatic, amide, and ester derivatives, and involves themolysis in an inert solvent to generate the nitrile oxide with con-commitant expulsion of carbon dioxide and alkanol. Other reactions leading to furoxans via nitrile oxides include treatment of a-bromo-a-nitrotoluene with triphenylphosphine <84TL2029), nitrosation... 

It is worthy of note that o-nitrotoluene is not brominated by this method even at temperatures up to 200°—an interesting example of steric hindrance. The m-compound, on the other hand, gives a 20% yield of the bromo-compound. 

Bromo-2-nitrosopropane, AB73 a-Bromo-2-nItrotoluene, AJ39 a-Bromo-3-nitrotoluene, AJ O a-Bromo-U-nitrotoluene, AJ l... 

Bromo-5-nitrotoluene, AJ38 5-Bromo-2-nitro-m-xylene, AM S... 

The aldehydes 3 were synthesized either by Vilsmeyer formyladon of 2 or by reaction of 4-fluorobenzaldehyde with a secondary amine (20). The stilbenes 4 were formed from the corresponding 4-dialkylamino-benzaldehydes either by the Homer-Emmons reaction with 4-nitrobenzyl-(diethyl)phosphonate (prepared by the Arbuzov reaction of a-bromo-4-nitrotoluene) or with 4-methylsulfonylbenzyl(diethyl)phosphonate (prepared in three steps from 4-methylthiobenzylaicohol) (21). A few nitrostilbene compounds were synthesized by heating aldehyde 3 with 4-nitrophenylacetic acid in the presence of piperidine. 

The addition of the anion of a-bromo-a-nitrotoluene (564) to cyclohexene gave the hexahydro derivative (565) of 3-phenyl-l,2-benzisoxazole (75TL2131). An unusual hexahydro derivative (566) was produced by the bis addition of benzonitrile A-oxide to benzoquinone (67AHC(8)277). 

A. 2-Bromo-4-nitrotoluene. In a 200-ml. three-necked, round-bottomed flask provided with an efficient reflux condenser bearing a suitable trap for absorbing hydrogen bromide, a 100-ml. separatory funnel, and a ball-joint or mercury-sealed mechanical stirrer are placed 68.5 g. (0.5 mole) of -nitrotoluene (Note 1) and 1.0 g. of iron powder. The mixture is heated to 75-80° by means of a water bath, vigorous stirring is begun, and 30.5 ml. (92.0 g., 0.57 mole) of bromine is added over the course of 30 minutes. After the addition of bromine is complete, the reaction mixture is maintained at 75-80° with continuation of stirring for an additional 1.5 hours. 

B. 2-Bromo-3-methylbenzoic acid. Caution This procedure must be carried out in a hood with a good draft, because poisonous hydrogen cyanide gas is evolved. In a 5-1. round-bottomed flask are placed 90 g. of potassium cyanide, 900 ml. of 2-ethoxyethanol (Note 3), 850 ml. of water, and the moist 2-bromo-4-nitrotoluene obtained above. A reflux condenser is attached, and the mixture is boiled for 16 hours (Note 4). To the hot, dark-red solution is then added 1.51. of water, and the mixture is acidified with concentrated hydrochloric acid. (Caution Hydrogen cyanide is evolved.) The acidified mixture is boiled for 15 minutes to expel hydrogen cyanide and then allowed to cool to 35-40°. Five grams of diatomaceous earth is stirred in, and the mixture is filtered through a Buchner funnel precoated with a little diatomaceous earth. The solid is discarded, and the filtrate is extracted three times with 200-ml. portions of chloroform. The chloroform extracts are combined and extracted with three 100-ml. portions of 5% ammonium carbonate solution. The basic extracts are combined, acidified with concentrated hydrochloric acid, and cooled in an ice bath. The oil which first forms soon crystallizes. 

The hot mixture of 2-bromo-4-nitrotoluene and 1% sodium hydroxide solution should be stirred vigorously during cooling in order to avoid obtaining the product as a solid cake. If stirring is omitted, subsequent treatment is less convenient. 

Although 2-bromo-4-nitrotoluene has been obtained by several routes, it is most easily prepared by bromination of />-nitro-toluene.2 The procedure given is adapted from that described by Cavil .3 2-Bromo-3-methylbenzoic acid has not been prepared by any other means evidence for its structure is presented elsewhere.4... 

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